Deletion of the yeast homologue of frataxin, YFH1, results in mitochondrial iron accumulation and respiratory deficiency (petite formation). We used a genetic screen to identify mutants that modify iron-associated defects in respiratory activity in Deltayfh1 cells. A deletion in the peroxisomal citrate synthase CIT2 in Deltayfh1 cells decreased the rate of petite formation. Conversely, overexpression of CIT2 in Deltayfh1 cells increased the rate of respiratory loss. Citrate toxicity in Deltayfh1 cells was dependent on iron but was independent of mitochondrial respiration. Citrate toxicity was not restricted to iron-laden mitochondria but also occurred when iron accumulated in cytosol because of impaired vacuolar iron storage. These results suggest that high levels of citrate may promote iron-mediated tissue damage.
机构:
Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo, Brazil
Barros, MH
Nobrega, FG
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Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo, Brazil
机构:
Univ Utah, Sch Med, Dept Pathol, Div Cell Biol & Immunol, Salt Lake City, UT 84132 USAUniv Utah, Sch Med, Dept Pathol, Div Cell Biol & Immunol, Salt Lake City, UT 84132 USA
Chen, OS
Kaplan, J
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Univ Utah, Sch Med, Dept Pathol, Div Cell Biol & Immunol, Salt Lake City, UT 84132 USAUniv Utah, Sch Med, Dept Pathol, Div Cell Biol & Immunol, Salt Lake City, UT 84132 USA
机构:
Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo, Brazil
Barros, MH
Nobrega, FG
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h-index: 0
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Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508900 Sao Paulo, Brazil
机构:
Univ Utah, Sch Med, Dept Pathol, Div Cell Biol & Immunol, Salt Lake City, UT 84132 USAUniv Utah, Sch Med, Dept Pathol, Div Cell Biol & Immunol, Salt Lake City, UT 84132 USA
Chen, OS
Kaplan, J
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h-index: 0
机构:
Univ Utah, Sch Med, Dept Pathol, Div Cell Biol & Immunol, Salt Lake City, UT 84132 USAUniv Utah, Sch Med, Dept Pathol, Div Cell Biol & Immunol, Salt Lake City, UT 84132 USA